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Clinical Interpretation Challenges of Germline-Shared Somatic Variants in Cancer

Kyoung-Jin Park¹

¹Department of Laboratory Medicine & Genetics, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Gyeongsangnam-do, Korea.

Laboratory Medicine

|June 29, 2021

Abstract

Objective:

To investigate the interpretation differences of germline-shared somatic variants.

Methods:

A total of 123,302 COSMIC variants associated with hematologic malignant neoplasms were used. The pathogenicity and actionability of shared variants were analyzed based on the standardized guidelines.

Results:

The overall frequency of variants shared in ClinVar/HGMD and COSMIC was 10%. The pathogenicity of 54 shared variants was pathogenic/likely pathogenic (P/LP; n = 30), variants of unknown significance (n = 3), and benign/likely benign (n = 21). In total, 30 P/LP variants were reclassified to tier I/tier II (83%) and tier III (17%) variants.

Conclusions:

This is the first study about different clinical interpretations of shared variants based on the current standard guidelines. This study takes a meaningful step in bridging the interpretation gap between the somatic and germline variants.

Keywords:

actionability germline interpretation pathogenicity somatic variant

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